Q&A. If bisantrene was such a good drug why was it abandoned?

This is a very important, but complex question to answer.

1. Good drug are often abandoned for non-clinical reasons. Something that is not well understood by those outside the biotech/pharma space is that good drugs are dropped all the time for reasons that have nothing to do with how well they work. The table below lists all the reasons why drugs are terminated in development. You can see from this data that more than 25% are dropped for non-clinical reason, the most common being rationalization of a company’s portfolio. Good drug, wrong company problem.


2. The original discover of bisantrene got into serious financial difficulties during bisantrene's development. Bisantrene was discovered and developed by Lederle which was a division of American Cyanamid. In the 1980s American Cyanamid started to get in financial difficulty. It was a large bulk chemical company (like Du Pont) that had pollution sites (superfund) that the USA EPA sued to get them to these cleaned up. They spent the 1980s spinning off various divisions and assets trying to stay afloat. Finally, the bulk chemical market collapsed in the 1990s recession and they ran out of money and were eventually bought up by American Home Products.

3. AML was a very small market in the 1980s. Today we are used to new cancer drugs selling for hundreds of thousand of dollars (or more), but back in the 1980s this wasn’t the case. AML is a relatively rare disease (thankfully), so the market back then for AML was quite small – maybe $10 million a year total. This wasn’t considered large enough market to support the development of a drug like bisantrene on its own.

4. Lederle were most interested in developing bisantrene for breast cancer, but they designed the wrong trial. The major market Lederle was concentrating on for bisantrene was breast cancer. They ran a large, US Phase III trial in the late 1980s where they compared bisantrene to doxorubicin and idarubicin (two existing drugs). While they found that bisantrene was just as efficacious as doxorubicin (better than idarubicin) and much safer (23% of the patients given doxorubicin suffered heart failure and only 4% given bisantrene did), they designed the trial as a superiority trial. This meant that even though bisantrene was just as good a doxorubicin (but much safer) the trial didn’t meet its endpoints. If they had designed and run the trial as a non-inferiority trial (where you try to show your drug is just as good as the existing drug(s), but safer, they would have been able to gain FDA approval. After this failure Lederle were faced with running a new large and expensive Phase III trial just when their parent company ran out of money. All rather unlucky.

Given all this it is not surprising that bisantrene was dropped – it certainly wasn’t because bisantrene was no good.